Memory CD8+ T cells specific for a single immunodominant or subdominant determinant induced by peptide-dendritic cell immunization protect from an acute lethal viral disease.
J Virol. 2012 Jun 27;
Authors: Remakus S, Rubio D, Ma X, Sette A, Sigal LJ
The antigens recognized by individual CD8(+) T cells are small peptides bound to MHC class I molecules. The CD8(+) T cell response to a virus is restricted to several peptides and the magnitude of the effector as well as memory phase of the response to the individual peptides is generally hierarchical. The peptide eliciting a stronger response is called immunodominant (ID) and those with smaller responses are termed subdominant (SD). The relative importance of ID and SD determinants in protective immunity remains to be fully elucidated. We have previously shown that multispecific memory CD8(+) T cells can protect susceptible mice from mousepox, an acute lethal viral disease. It remained unknown, however, whether CD8(+) T cells specific for single ID or SD peptides can be protective. Here we demonstrate that immunization with dendritic cells pulsed with ID and some but not all SD peptides induced memory CD8(+) T cells that were fully capable of protecting susceptible mice from mousepox. Additionally, while natural killer (NK) cells are essential for the natural resistance of non-immune C57BL/6 (B6) to mousepox, we show that memory CD8(+) T cells of single specificity also protect B6 mice depleted of NK cells. This suggests it is feasible to produce effective anti-viral CD8(+) T cell vaccines using single CD8(+) T cell determinants and that NK cells are no longer essential when memory CD8(+) T cells are present.
PMID: 22740418 [PubMed - as supplied by publisher]